A principal characteristic of metastatic tumors is their invasiveness. After the cells detach from the primary tumor, they must cross membrane barriers to reach other target sites. We are studying molecular events of an aspect of this process, the chemotactic responsiveness of these cells to certain stimuli. Using a human melanoma cell line, we have found that these cells migrate in response to a material in their conditional media which has a Mr of about 20 KD and does not appear to be identical to other known attractants. The material may have plasminogen activator activity. These cells also respond to the peptides F Met-Leu-Phe and bombesin. Additionaly, we have found that a highly metastatic murine melanoma cell line selected from a subline of cells is markedly more chemotactically responsive than a poorly metastatic line from the same subline.